EP0200591B1 - Verfahren zur Herstellung von reinen Androst-2-enderivaten - Google Patents
Verfahren zur Herstellung von reinen Androst-2-enderivaten Download PDFInfo
- Publication number
- EP0200591B1 EP0200591B1 EP86400622A EP86400622A EP0200591B1 EP 0200591 B1 EP0200591 B1 EP 0200591B1 EP 86400622 A EP86400622 A EP 86400622A EP 86400622 A EP86400622 A EP 86400622A EP 0200591 B1 EP0200591 B1 EP 0200591B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- radical
- androstene
- pure
- isomer
- mixture
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 0 CC1(C(CC2)C(CC3)C4*2C(*)(*)CC4)C3(C)C=CC(*)C1 Chemical compound CC1(C(CC2)C(CC3)C4*2C(*)(*)CC4)C3(C)C=CC(*)C1 0.000 description 2
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
- C07J31/003—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring the S atom directly linked to a ring carbon atom of the cyclopenta(a)hydrophenanthrene skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J11/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 3
Definitions
- a process for obtaining an androstenic compound A-2 in the pure state from a mixture of A-2 (3) and A-3 (4) androstene characterized in that a mixture is subjected androstenes corresponding to the general formula in which the dotted line symbolizes a double bond in position 2 (3) or in position 3 (4)
- R represents a free hydroxyl, esterified by an organic acid having from 1 to 10 carbon atoms, or etherified by an alkyl or tetrahydro-pyranyl radical
- R ' represents hydrogen, a lower alkenyl radical, a lower alkynyl radical, a radical lower alkyl, a phenyl radical or a cycloalkyl radical or R and R 'together form the oxygen of a ketone function
- the wavy line indicates an a or 13 orientation to the action of a pure sulfonating agent or in an inert solvent in the possible presence of a dehydrating agent to obtain an A-3 androsenyl 2-s
- the present invention is based on the surprising observation that it is possible to sulfonate selectively in anhydrous medium the androstenic isomer A-3 in order to obtain a strongly acid derivative of water-soluble, corresponding to the general formula II wherein the substituents R and R 'have the meanings previously provided.
- This derivative is then easily eliminated by anion exchange resins in an alcoholic medium or simply by pouring the reaction medium into water, an operation which causes the insoluble, unconverted steroid A-2 to crystallize, and to dissolve the sulfonated steroid A-3. After filtration, washing with water and drying, the pure steroid A-2 is obtained.
- Sulfonation with sulfuric acid, pure or in solution is carried out in an inert solvent such as, for example, acetic acid, dichloromethane, chloroform, dioxane, in the presence of a dehydrating agent such as anhydride d alkylcarboxylic acid such as acetic anhydride or propionic anhydride.
- the temperature of the reaction medium can vary from 5 ° C. to + 50 ° C. This reaction time, from a few minutes to several days, depending on the operating conditions.
- the structural analysis of the purified steroid was carried out by infrared spectrophotometry and by nuclear magnetic resonance of the proton.
- the olefinic protons in C2 and C3 appear in the form of a singlet widened to 334 Hz (half-width 5 Hz) while for the A-3 androstenic derivatives, the olefinic protons appear in the form of 4 masses between 312 and 348 Hz.
- the invention also relates to the A-3-androstenyl-2-sulfonic acids of general formula II, formed during the execution of the process according to the invention.
- the reaction medium was poured quickly into 300 ml of anhydrous ethanol, and after 2 hours of stirring, the solution obtained was passed through a column loaded with 50 g of anion exchange resin, DOWEX® AG2 X8 (in the form OH-) previously dehydrated with anhydrous ethanol. After passing the solution, the column was washed with 100 ml of ethanol, the combined effluents and washing liquors were evaporated to dryness under vacuum.
- anion exchange resin DOWEX® AG2 X8 (in OH- form), previously dehydrated with methanol and 30 minutes at room temperature, were added. It is filtered, the resin is washed with 50 ml of methanol and the filtrate and the combined washing liquids are evaporated to dryness.
- the A-2 androstenic derivatives of general formula IV are drugs which behave, according to the conditions of use, as brakers or on the contrary pituitary stimulants.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Claims (8)
die punktierte Linie eine Doppel Bindung in Stellung 2(3) oder 3(4) bedeutet
R für eine freie, mit einer organische C1-C10 Säure esterifierte oder mit einem Alkyl Radikal oder einem Tetrahydropyranyl etherifierte Hydroxyl steht R' Wasserstoff, ein niedrig Alkenyl Radikal, ein niedrig Alkynyl Radikal, ein niedrig Alkyl Radikal, ein Phenyl Radikal ist
oder R und R' zusammen das Sauerstoff einer ketonische Funktion bilden
und die wellenförmige Linie eine a oder β räumliche Orientierung bedeutet
auf die Wirkung eines reinen oder in einem inerten Lösungsmittel Sulfonierungsmittel gegebenenfalls in Anwesenheit eines Dehydratisierungsmittel unterworfen wird, um eine A-3 Androstenyl 2-sulfonsäure der allgemeinen Formel ll
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AT86400622T ATE40139T1 (de) | 1985-04-29 | 1986-03-25 | Verfahren zur herstellung von reinen androst-2enderivaten. |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR8506471 | 1985-04-29 | ||
FR8506471 | 1985-04-29 |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0200591A1 EP0200591A1 (de) | 1986-11-05 |
EP0200591B1 true EP0200591B1 (de) | 1989-01-18 |
Family
ID=9318768
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP86400622A Expired EP0200591B1 (de) | 1985-04-29 | 1986-03-25 | Verfahren zur Herstellung von reinen Androst-2-enderivaten |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP0200591B1 (de) |
AT (1) | ATE40139T1 (de) |
DE (1) | DE3661832D1 (de) |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3098851A (en) * | 1961-11-20 | 1963-07-23 | Searle & Co | 17alpha-alkynyl-2beta-halo-5alpha-androstane-3alpha, 17beta-diols, esters thereof, and intermediates thereto |
GB1492746A (en) * | 1974-01-17 | 1977-11-23 | Theramex | Androstane derivatives and compositions containing them |
EP0066001B1 (de) * | 1981-06-02 | 1986-05-14 | Laboratoire Théramex | Androstenen enthaltenden pharmazeutische Zusammensetzungen |
-
1986
- 1986-03-25 DE DE8686400622T patent/DE3661832D1/de not_active Expired
- 1986-03-25 EP EP86400622A patent/EP0200591B1/de not_active Expired
- 1986-03-25 AT AT86400622T patent/ATE40139T1/de not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
EP0200591A1 (de) | 1986-11-05 |
DE3661832D1 (en) | 1989-02-23 |
ATE40139T1 (de) | 1989-02-15 |
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